{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:18:08Z","timestamp":1788337088681,"version":"build-2803163510"},"reference-count":38,"publisher":"World Scientific Pub Co Pte Ltd","issue":"06","funder":[{"name":"the Ministry of Science and ICT; the International Cooperative R&D Program","award":["P0019158"],"award-info":[{"award-number":["P0019158"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Chin. Med."],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Phytoestrogens derived from natural products have emerged as potential alternatives to hormone replacement therapy (HRT) for alleviating menopausal symptoms with reduced adverse effects. However, the therapeutic potential and mechanistic basis of flaxseed-derived lignan secoisolariciresinol diglucoside polymer (SDGP) remain largely unexplored. This study aimed to investigate the synergistic effects of SDGP and a linusorb mixture (LOMIX) on menopausal symptoms and to elucidate their underlying molecular mechanisms. Estrogen receptor (ER) activation was evaluated using ERE-luciferase reporter assays and Western blot analysis in MCF-7 cells. Anti-osteoclastogenic effects were assessed in RANKL-induced RAW264.7 cells. An ovariectomized (OVX) rat model was used to examine in vivo efficacy on reproductive tissues and bone metabolism. Co-treatment with SDGP and LOMIX synergistically enhanced ER\u03b1\/ER\u03b2 phosphorylation and Akt activation, leading to increased transcription of ER target genes. The combination also suppressed osteoclast differentiation by inhibiting NF-\u03baB and MAPK signaling pathways, including c-Fos and NFATc1. In OVX rats, oral administration of the mixture restored vaginal cornification and uterine morphology, and significantly improved trabecular bone structure and bone mineral density. Notably, these effects were achieved without significant alterations in circulating estrogen, FSH, or LH levels. The combination of SDGP and LOMIX alleviates menopausal symptoms through non-hormonal activation of ER signaling and inhibition of osteoclastogenesis. These findings suggest a promising phytotherapeutic strategy for managing postmenopausal disorders with reduced risk of hormone-related side effects.<\/jats:p>","DOI":"10.1142\/s0192415x26500692","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:13:03Z","timestamp":1786518783000},"page":"1853-1873","source":"Crossref","is-referenced-by-count":0,"title":["Flaxseed and Linusorb Synergistically Ameliorate Menopausal Symptoms Through Non-Hormonal Activation of Estrogen Receptors and Suppression of Osteoclastogenesis"],"prefix":"10.1142","volume":"54","author":[{"given":"Won Young","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hye","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seul Bi","family":"Lee","sequence":"additional","affiliation":[{"name":"Ingredient R&D Center, Kolmar BNH Co., Ltd., Seoul 06800, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Ingredient R&D Center, Kolmar BNH Co., Ltd., Seoul 06800, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn Young","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Plant Sciences, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J. T.","family":"Reaney","sequence":"additional","affiliation":[{"name":"Department of Plant Sciences, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7937-0167","authenticated-orcid":false,"given":"Byong Chul","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5073-2619","authenticated-orcid":false,"given":"Jongsung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"},{"name":"Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-9927","authenticated-orcid":false,"given":"Jae Youl","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"},{"name":"Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"219","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"S0192415X26500692BIB001","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20200167"},{"key":"S0192415X26500692BIB002","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24203700"},{"key":"S0192415X26500692BIB003","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.153982"},{"key":"S0192415X26500692BIB004","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2017.07.006"},{"key":"S0192415X26500692BIB005","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31709-X"},{"key":"S0192415X26500692BIB006","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1920-9_10"},{"key":"S0192415X26500692BIB007","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.010843"},{"key":"S0192415X26500692BIB008","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29757"},{"key":"S0192415X26500692BIB009","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2018.05.018"},{"key":"S0192415X26500692BIB010","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2013.08.010"},{"key":"S0192415X26500692BIB011","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-020-01164-6"},{"key":"S0192415X26500692BIB012","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232415482"},{"key":"S0192415X26500692BIB013","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001058"},{"key":"S0192415X26500692BIB014","doi-asserted-by":"publisher","DOI":"10.11005\/jbm.2015.22.1.23"},{"key":"S0192415X26500692BIB015","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29423-5"},{"key":"S0192415X26500692BIB016","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.802959"},{"key":"S0192415X26500692BIB017","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03939-7"},{"key":"S0192415X26500692BIB018","doi-asserted-by":"publisher","DOI":"10.1159\/000371845"},{"key":"S0192415X26500692BIB019","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-021-06380-5"},{"key":"S0192415X26500692BIB020","first-page":"321","volume":"97","author":"Paladine H.L.","year":"2018","journal-title":"Am. Fam. Physician"},{"key":"S0192415X26500692BIB021","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113385"},{"key":"S0192415X26500692BIB022","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyz174"},{"key":"S0192415X26500692BIB023","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1821"},{"key":"S0192415X26500692BIB024","doi-asserted-by":"publisher","DOI":"10.3390\/biom10060859"},{"key":"S0192415X26500692BIB025","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-03093-x"},{"key":"S0192415X26500692BIB026","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154739"},{"key":"S0192415X26500692BIB027","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2022.2119363"},{"key":"S0192415X26500692BIB028","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0676.2001.210507.x"},{"key":"S0192415X26500692BIB029","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206769"},{"key":"S0192415X26500692BIB030","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112975"},{"key":"S0192415X26500692BIB031","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25245881"},{"key":"S0192415X26500692BIB032","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-4337.2009.00105.x"},{"key":"S0192415X26500692BIB033","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(02)00305-2"},{"key":"S0192415X26500692BIB034","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2014.05.014"},{"key":"S0192415X26500692BIB035","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14146-6"},{"key":"S0192415X26500692BIB036","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.895916"},{"key":"S0192415X26500692BIB037","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010536"},{"key":"S0192415X26500692BIB038","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2022.68.1.16"}],"container-title":["The American Journal of Chinese Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.worldscientific.com\/doi\/pdf\/10.1142\/S0192415X26500692","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:46:25Z","timestamp":1788335185000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.worldscientific.com\/doi\/10.1142\/S0192415X26500692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":38,"journal-issue":{"issue":"06","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1142\/S0192415X26500692"],"URL":"https:\/\/doi.org\/10.1142\/s0192415x26500692","relation":{},"ISSN":["0192-415X","1793-6853"],"issn-type":[{"value":"0192-415X","type":"print"},{"value":"1793-6853","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}